Statins are a class of cholesterol lowering medications proven effective for attaining healthy cholesterol and lipoprotein levels, while also indicated for a number of other health conditions, e.g. lowering heart disease risk, vascular protection. As a result, statin use has increased in recent years. Skeletal muscle weakness and pain are occasional side effects of statin use (1-7%) and in rare cases severe muscle destruction (rhabdomyolysis) may result. Accumulating evidence suggests that the prevalence of statin effects on skeletal muscle may very well be underestimated. Statins can cause structural and functional impairments in skeletal muscle by inhibiting cholesterol synthesis and the intermediate products. Statin effects include myocyte apoptosis, decreased cell membrane integrity, mitochondrial myopathy, diminished cytoskeletal integrity and diminished muscle repair. These may consequently result in reduced muscle function including strength loss, increased susceptibility to damage, and diminished muscle aerobic metabolism. Currently serum creatine kinase (CK) or muscle biopsies are used to verify statin induced myopathy. While CK can be easily assessed, it is not necessarily elevated in statin users with myalgia or myopathy. In this pilot project, molecular imaging with NMR (nuclear magnetic resonance) will be used to measure skeletal muscle integrity and function before and during statin treatment. Aim 1 will examine the effect of statins on skeletal muscle cell membrane turnover by non-invasively measuring phosphorus metabolites with NMR, in particular muscle and blood phosphodiesterase (PDE). Elevated PDE appears in tumors as well as skeletal muscle of individuals with muscle related disorders presumably from increased cell turnover. Muscle PDE is also elevated in statin users. Aim 2 will examine the effects of statins on mitochondrial function by measuring the change in muscle aerobic capacity primarily with phosphorus NMR and muscle fatigue. Aim 3 will examine the effect of statins on skeletal muscle function including changes in maximal strength and muscle damage (with NMR). Twenty-five healthy individuals will be tested before and during 4 weeks of statin use (80-mg atorvastatin calcium). Aims 1 and 3 will also be evaluated in a patient population. Through this pilot study we will determine the utility of using NMR to non-invasively assess statin- induced myopathy and to quantify muscle functional declines with statin use. NMR may be particularly relevant for identifying individuals for whom the benefits of statins might otherwise be blunted by muscle effects. PUBLIC HEALTH RELEVANCE. With the widespread and ever increasing use of statins (cholesterol lowering medications), there is a true need to understand the side effects of statin use including the true functional consequences to skeletal muscle. These studies are designed to measure changes in muscle health and function without using invasive procedures. In addition, these studies are designed to evaluate a novel measure of statin induced muscle problems.